The person-identity network (PIN), which underlies the recognition and identification of familiar people, is considered within the domain of the long-term semantic memory system. Knowledge of its neural underpinnings, derived primarily from studies of brain-lesioned patients, suggest that the PIN may have important and unique features in comparison to the general object semantic system. This five-year proposal consists of seven event-related functional MRI experiments designed to better understand the neurobiological substrates of the PIN, effects of healthy aging on the PIN, and the identification of PIN-related brain activation patterns that may identify the earliest stages of abnormality in individuals at-risk for developing Alzheimer's disease (AD). In Aim 1, two experiments in healthy young participants will: (1) identify common and unique neural systems associated with distinct modes of access (faces versus names) to the PIN, and (2) compare retrieval from the PIN with retrieval from other semantic categories (familiar landmarks). In Aim 2, we will examine the effect of healthy aging and low genetic risk for developing AD on retrieval from the PIN by: (1) contrasting activation patterns produced by younger and older participants for name and face recognition, and (2) comparing activation patterns for recent and remote famous people to examine the neural substrates of a possible temporal gradient in remote memory. In Aim 3, the neural representation of the PIN will be examined in older healthy participants with a genetic susceptibility toward developing AD by virtue of having a sibling with AD and possessing at least one apolipoprotein E e4 (APOE e4) allele. The neural significance of being at-risk for developing AD will be examined in two PIN experiments involving: (1) famous face/name recognition, and (2) temporal gradient. These PIN studies will determine whether the presence of the APOE e4 allele is associated with a unique activation pattern that may serve as an early marker for subsequent cognitive decline. In Aim 4, older participants will undergo a second neuroimaging study after three years to assess longitudinal changes in brain activation patterns associated with the PIN as a function of AD at-risk status. Results of this project are expected to provide novel insights into our understanding of the neural systems that mediate retrieval from the PIN, and the neurobiological substrates of memory pathology that may presage abnormal age-related memory functioning.